Pharmacological Management of Heart Failure PDF

Heart Failure Complex syndrome with many causes Two major types 1. Diastolic Failure structural or functional impairment of ventricular filling Increased resistance to filling CO and Ventricular filling ( preload ) decreased, EF may be preserved...

Heart Failure Complex syndrome with many causes Two major types 1. Diastolic Failure structural or functional impairment of ventricular filling Increased resistance to filling CO and Ventricular filling ( preload ) decreased, EF may be preserved or 2. Systolic failure Inefficient ejection of blood Right or left sided or both Reduced ejection fraction and cardiac enlargement Causes numerous CAD, Ischemia and MI Chronic pressure overload ( increased afterload) HTN, aortic stenosis Chronic volume overload Many compensatory mechanisms May be helpful initially Increase workload over time Cardiac remodeling Enlargement, hypertrophy initially, dilation and wall thinning,  Systolic failure EF< 40 percent Incidence increases with age Mortality rate high 50 % within 5 years of diagnosis Compensatory mechanisms numerous Hypertrophy, dilation or both Activation of neurohumoral system SNS ( Catecholamines) RAA Poor outcomes correlated with amount of neurohumoral activation Drugs that improve outcomes in general reduce these factors Types of heart failure and common causes Early compensations Approaches to Treatment Reduce volume Reduce afterload Increase contractility Stages and classification Positive Inotropic agents Cardiac glycosides ( Digoxin) PDE inhibitors Beta agonists Dobutamine and others IN general These drugs improve symptoms and quality of life, but not 5 year survival Some outcomes worse Not recommended as first line agents any longer Digoxin  Digoxin Inhibits Na/K ATPase pump Specifically competes with K for binding and inhibition Why hypokalemia can potentiate dig toxicity Sodium accumulates in cells Sodium calcium exchanger stimulated Increases intracellular calcium and contractility Dig also decreases AV nodal conduction Can be used to treat arrhythmias, but other agents usually preferred Use in heart failure Positive inotropic actions Although symptomatic improvement, with reduced hospitalization there is no benefit to survivability Was the “Gold Standard” for decades Has been replaced by ACE inhibitors, beta blockers for systolic CHF  Kinetics half life of 30-33 hours Steady state requires approximately 5 half lives About a week Loading dose often given Narrow TI and numerous drug interactions Verapamil , potassium sparing diuretics, amiodarone and many many more Hypomagnesaemia, potassium abnormalities, hypercalcemia, acid base status Renal function , respiratory function, thyroid levels, underlying heart disease , etc all can alter a patient’s sensitivity to dig.  Toxicity Rhythm disturbances including AV block and premature ventricular depolarization Can result in life threatening V-tach Monitoring and dosage adjustments can increase safety Digoxin antibody ( Digibind, Digifab, DigiTab) Can be used as antidote for dig toxicity PDE inhibitors Milrinone (Primacor) PDE inhibitor Increases intracellular calcium and contractility Used in acute failure to maintain circulation Short term parenteral drugs only Not used post MI Pro-arrhythmogenic after acute MI Only in failure not associated with MI Inamrinone(Inacor) Positive inotrope and vasodilator IV for short term management of acute heart failure Increases cardiac output Associated with arrhythmias and thrombocytopenia Used primarily when other drugs fail and for short periods of time Long term use associated with worse outcomes Dopamine receptor and Beta agonists Dopamine (Dopastat, Intropin) Only IV Increases renal blood flow , inotropic effects Acts on dopamine receptors , alpha and beta receptors Low doses bind dopamine Rs Binding: Dopamine >Beta > Alpha As dose increases , beta and then alpha effects Short term management of severe chronic failure , refractory to other agents Dobutamine (Dobutrex) Synthetic Beta 1 selective receptor agonist Increases intracellular calcium Increases contractility Does not bind dopamine receptors but renal blood flow ( and therefore urine output) may increase due to increasing cardiac output Binds Beta 2 receptors (vasodilation) , alpha 1 receptors less Symptomatic benefit in acute decompensated failure Intermittent recurring IV drips may increase mortality Recommendation is continuous IV Infusions only to relieve symptoms in end stage disease ACE inhibitors First line agents Improve outcomes ( 5 year survival) Reduce afterload( via vasodilation), lower volume (aldosterone inhibition) No reflex tachycardia or contractility increases Increase bradykinin Further vasodilatory effects Captopril(Capoten), enalapril, Lisinopril (Zestril), Benazepril, and others Captopril is the parent compound Remaining are prodrugs Enalaprilat is the active form of Enalapril Eliminated by kidneys Dose adjustments in renal failure Many uses First line agents for heart failure, beneficial for mild, moderate, and severe forms Drug of choice for post MI CHF patients Preserve left ventricular function long-term Adverse effects Hyperkalemia( requires monitoring), dry cough, angioedema ( rare but greater in women and African Americans) CI in pregnancy  ARBS Valsartan(Diovan), Losartan (Cozaar) and Candesartan(Atacand) Valsartan and Candesartan FDA approved for Tx of heart failure in patients intolerant of ACE Inhibitors Reduces symptoms, hospitalizations and has shown survival benefit  Vasodilators Increase venous capacitance and decrease arterial resistance Dilate veins and arteries Reduce afterload, preload and heart work NTG and Nitroprusside for severe disease Hydralazine and ISDN in combo (oral form) May be useful in chronic congestive failure esp in patients intolerant of ACE inhibitors and African Americans Hydralazine dilates arterioles primarily Used preferentially in patients with fatigue and low ventricular output Diuretics Used for both systolic and diastolic failure Relieve pulmonary and peripheral edema, reduce dyspnea and symptoms of volume overload Decrease blood volume and preload HCTZ useful in mild heart failure Loop diuretics more effective Furosemide is the diuretic of choice for heart failure IV forms used in acute heart failure Potassium sparing diuretics Used primarily in combination with thiazides or loop diuretics to offset electrolyte abnormalities However spironolactone(Aldactone) has shown benefit in reducing cardiac remodeling Caution with drugs that increase potassium levels ACE inhibitors, and others Beta adrenergic blocking drugs Decrease cardiac output Inhibit compensatory activation of RAA system Useful in mild to moderate and even severe heart failure Especially with coexisting conditions they treat Arrhythmias, migraines, angina , etc Adverse effects Lethargy, depression, fatigue, hypotension, and rebound HTN if abruptly withdrawn Avoid if possible in asthmatics Beta blockers were contraindicated at one time for all stages of heart failure Many patients respond favorable and better outcomes Mortality reduction in class II and III  Beta blockers used in heart failure Carvedilol (Coreg) , has both alpha and beta blocking properties Greater affinity for beta receptors than alpha receptors Reduces adverse effects of elevated catecholamines in response to decreased output Heart rate reduction ( decreases workload) Reduces remodeling in response to increased catecholamines Metoprolol(Toprol) also used , long acting form Bisoprolol (Cardicor) Situations or conditions that might prevent use Nesiritide(Natrecor) IV form of human brain natriuretic peptide (BNP) Normally produced in response to increases in ventricular volume Causes arterial and venous dilation Inhibits ADH and aldosterone via RAA inhibition Promotes fluid and sodium loss Indicated for acute Treatment of decompensated congestive heart failure Reduces symptoms …dyspnea, fatigue Hypotension and syncope Sacubitril (Entresto) Neprilysin antagonist Neprilysin functions normally to degrade BNP and ANP Entresto is Sacubitril and Valsartan in combination (ARNI) Approved for treatment of systolic failure … heart failure with reduced ejection fraction Data suggests that ARNI is superior to ACE inhibitor or ARB alone in reducing mortality ARNI should NOT be combined with an ACE inhibitor And should not be given to anyone with a history of angioedema  link to ACC/AHA 2017 update treatment guidelines for h eart failure